Insulin and cyclic AMP have been linked to the regulation of mammary tumor growth and regression. Approximately 70 percent of primary DMBA-induced mammary tumors regressed when tumor bearing rats were made diabetic after treatment with streptozotocin. Following insulin withdrawal, significant increases were observed in the cyclic AMP levels, cyclic AMP binding and cyclic AMP-dependent protein kinase activities, both in the cytosol and nuclei. The regulation of the cyclic AMP system by insulin and other hormones is being investigated at the levels of the cyclic AMP phosphodiesterases and will be extended to include adenylate cyclase.